Treatment of vascular injury

Abstract

Patients suffering vascular injury as a result of balloon catheterization or the like are treated with medicaments containing conjugates comprising a ligand, such as bFGF (or another FGF polypeptide), and a cytotoxic agent. The cytotoxic agent can be a ribosome-inactivating protein (RIP), such as saporin, which is attached to the ligand through a chemical bond or prepared as a recombinant DNA chimera. The medicament containing the conjugate is administered IV to patients after they have been treated for atherosclerosis in a manner which commonly results in vascular injury, particularly to the intima, and effectively prevents restenosis. The conjugate kills proliferating smooth muscle cells in the lumen of the blood vessels which surprisingly express large numbers of high-affinity bFGF receptors while not inhibiting the growth of endothelial cells.

We claim: 
     
       1. A method of preventing restenosis caused by smooth muscle cell proliferation in response to injury to the endothelial lining of blood vessel walls, which method comprises administering intravenously or locally an effective amount of a bFGF-saporin conjugate sufficient to prevent smooth muscle cell proliferation in the lumen of the blood vessel, while not inhibiting the regrowth of said endothelial lining. 
     
     
       2. The method of claim 1 wherein said amount administered is between approximately 0.01 mg and 100 mg of conjugate per kilogram of body weight per day. 
     
     
       3. The method of claim 1 wherein said amount administered is approximately 0.1 mg of conjugate per kilogram of body weight per day. 
     
     
       4. The method of claim 3 wherein said conjugate is administered intravenously. 
     
     
       5. The method of claim 4 wherein said conjugate is administered between 24 hours and six weeks after said injury. 
     
     
       6. The method of claim 2 wherein said conjugate is administered locally. 
     
     
       7. A method of preventing restenosis caused by smooth muscle cell proliferation in response to endotoxin damage to the endothelial lining or to damage from vascular surgery by balloon catheterization treatment, which method comprises intravenously administering an effective amount of FGF conjugated to a cytotoxic ribosome-inactivating protein, said amount of FGF-conjugate being sufficient to prevent smooth muscle cell proliferation in the lumen of the blood vessels while not inhibiting regrowth of the endothelial lining, said administering occurring between 24 hours and six weeks after damage.